1. Field of the Invention
The present invention relates to supersaturated solutions of ascorbic acid and compositions including such solutions. In addition, the present invention relates to supersaturated, yet stable, solutions of L-ascorbic acid and/or other physiologically acceptable isomers of ascorbic acid. More specifically, the invention relates to a chemically stable L-ascorbic acid and its isomeric forms, in solution, at very high concentration levels. The present invention further provides a method of forming chemically stable, supersaturated ascorbic acid solutions.
2. Description of the Prior Art
L-ascorbic acid (vitamin C) is a water-soluble, "red-ox" (reduction-oxidation) active carbohydrate. Physiologically, L-ascorbic acid functions as a reductive cofactor for enzymes that require transition metal ions in reduced form (such as CU.sup.+ and Fe.sup.+2) for optimum activity. Such enzymes include proline and lysine hydroxylases that are responsible for proper structure and function of skin collagen and elastin. This red-ox cofactor role is one mechanism by which L-ascorbic acid contributes to the maintenance of proper structural and functional integrity of tissues, such as in the epidermal and dermal layers of human skin. J. Soc. Cosmet. Chem., vol. 34, pages 439-451 (1983).
The red-ox properties of L-ascorbic acid also make it a good scavenger of reactive radicals, such as superoxide 0.sup.-2, hydroxyl HO.sup.-, peroxyl ROO.sup.- and alkoxyl RO.sup.- radicals. Such reactive radicals are generated in skin upon exposure to ultraviolet light or chemical initiators, such as singlet oxygen, ozone and peroxides. It has been found that by scavenging such reactive radicals, L-ascorbic acid protects the skin against oxidative damage and reduces consequent photoaging symptoms, such as dryness, wrinkling, irregular pigmentation and loss of elasticity. Advances in Free Radical Biology and Medicine, vol. 2, pages 419-444 (1986); British J. Dermatol., vol. 127, pages 247-253 (1992).
Despite its hydrophilic nature, L-ascorbic acid also has the ability to help regenerate the lipophilic antioxidant, tocopherol (vitamin E), from corresponding tocopheroxyl radicals. Chemistry Letters, vol. 6, pages 789-792 (1982). By regenerating tocopherol, L-ascorbic acid helps preserve the skin's endogenous, antioxidant defense mechanisms.
Because of the numerous beneficial properties attributed to L-ascorbic acid, its topical use is desired. However, the formation of a topical delivery system for L-ascorbic acid is difficult since L-ascorbic acid is stable only in solid form and at ambient temperatures. L-ascorbic acid decomposes in solubilized form, undergoing rapid and irreversible aerobic and anaerobic degradation. Int'l. J. Vit. Research, Suppl. vol. 27, pages 259-306 (1985); Bulletin Chem. Soc. Japan, vol. 46, pages 902-904 (1973).
Both aerobic and anaerobic degradation reduces the efficacy of ascorbic acid products. Known topical delivery systems that contain such degraded L-ascorbic acid have poor aesthetic qualities due to discoloration, undesired changes in viscosity, malodor and evolution of carbon dioxide gas bubbles. Decomposition of L-ascorbic acid in solution has virtually precluded its use in personal care products at meaningful and effective concentrations. Therefore, manufacturers are currently forced to add only ineffective amounts of L-ascorbic acid to topical products just to meet the demand in the market for products containing L-ascorbic acid.
The following reaction sequence shows the typical aerobic degradation of L-ascorbic acid: ##STR1##
The following reaction sequence shows the anaerobic degradation of L-ascorbic acid: ##STR2##
Attempts have been made to obtain stable solutions of L-ascorbic acid. For example, U.S. Pat. No. 2,179,978 to Elger describes solutions of L-ascorbic acid in anhydrous ethanol. The application to the skin of L-ascorbic acid dissolved in a water-free, undiluted alcohol solution, such as ethanol, is not practical since the alcohol contributes to dryness and chapping of the skin and, thus negates the positive effect of L-ascorbic acid.
Another attempt at stabilizing L-ascorbic acid in solution involved adding a sulfur-containing reducing agent, such as sulfur dioxide, sulfur-containing acids and/or salts capable of emitting sulfur dioxide. However, the emission of sulfur dioxide causes a pungent and very disagreeable odor that simulates rotting eggs.
L-ascorbic acid at a concentration of less than 0.5 percent by weight has been reported as having been added to ethanol, glycerin, propylene glycol, sorbitol, dextrose, sucrose and corn sugar. J. American Pharm. Assoc., vol. XLIV(4), page 241 (1955); Yakugaku Zashi (Japan), vol. 96(2), page 232 (1976). At such a concentration, L-ascorbic acid provides no significant benefits to skin. One reason for the use of such a low concentration of L-ascorbic acid is that using current technology more L-ascorbic acid could not be dissolved in such a media and maintained without precipitation of ascorbic acid.
U.S. Pat. No. 5,120,762 to Hanaoka et al. is directed to a stable sodium ascorbate powder. However, such a powder forms an unstable solution. It has also been reported that the addition of phenolic antioxidants, such as rutin, quercetrin, quercetin, methylchalcone and hesperidin, to L-ascorbic acid may stabilize L-ascorbic acid in solution (Referat Zhur. Khim., Biol. Khim., Abstract No. 1635 (1960). The reported stabilizing effects are questionable since phenolic antioxidants form colors in solution that indicate instability. Further, colored solutions are not aesthetically suitable for topical compositions.
Other additives that have been used in an effort to stabilize L-ascorbic acid in solution include oxalic acid, metaphosphoric acid, glutathione, thiourea and sodium diethyldithiocarbamate, Can. J. Research, vol. 28E, pages 19-32 (1950); proteins, Biochimie, vol. 56, page 1255-1267 (1974); and glycosaminoglycans, Int. J. Pharmaceut., vol. 107, pages 199-203 (1994).
Other attempts at stabilizing solutions of L-ascorbic acid have included the addition to L-ascorbic acid of calcium salt of quinic acid (Swiss Patent No. 2,140,989); benzoyl and veratroyl esters (U.S. Pat. No. 2,150,140); ester of histidine (U.S. Pat. No. 2,134,246); salts of iron, manganese, calcium, bismuth, arsenic, silver, gold, mercury, copper, zinc, aluminum or tin (Canadian Patent No. 375,573); aliphatic amine esters (U.S. Pat. No. 2,132,662); thiourea and the methyl and ethyl derivatives of thiourea (U.S. Pat. No. 2,297,212); and thioglycolic or thiolactic acid (Japanese Patent Application No. 5048). Efforts have even included sealing L-ascorbic acid solutions under nitrogen in vacuum ampoules sterilized with phenol. J. American Pharm. Assoc., vol. 35, page 363 (1946). The above attempts at providing a practical, aesthetically acceptable, stable, topical L-ascorbic acid in solution in which chemicals and bioactives are added to L-ascorbic acid, all have been unsuccessful.
Thus, the problem of L-ascorbic acid instability in solution remains unsolved for the practical delivery of effective levels of L-ascorbic acid in topical, personal care products.